Lymph node involvement is one of the most important clinical features to determine when managing colorectal cancer patients. Node-negative disease is often cured by surgery alone, whereas node-positive disease requires the administration of chemotherapy, and is associated with a decreased probability of cure. We have identified alterations to the p arm of chromosome 8, and gene expression changes which are correlated with positive lymph node status. This application seeks to determine if mutations in a novel 8p tumor suppressor gene, along with resulting gene expression alterations, are associated with recurrence among node-negative colorectal cancer patients. If successful, these tests will lead to improved ability to diagnose node-positive disease, and will significantly impact the clinical decisions made during the management o early stage colorectal cancer patients. PUBLIC HEALTH RELEVANCE: Patients with node-negative colorectal cancers can usually be cured by surgery alone, while patients with node-positive disease require additional chemotherapy or radiation therapy. The diagnosis of node-negative disease is sometimes wrong, and some patients are mistakenly undertreated. This application seeks to define the mechanism by which mutations in a novel tumor suppressor gene can cause colorectal cancers to metastasize to the regional lymph nodes. This will lead to genetic testing of tumors to prevent the accidental diagnosis of benign disease, and ultimately to novel strategies to manage patients with metastatic colorectal cancer.